Is transoral incisionless fundoplication (TIF) an answer to post-peroral endoscopic myotomy gastroesophageal reflux? A multicenter retrospective study.

BACKGROUND: The use of peroral endoscopic myotomy (POEM) for achalasia has a high incidence of post-procedural gastroesophageal reflux (GER). Transoral incisionless fundoplication (TIF) may be an ideal endoscopic treatment. We report our experience with the use of post-POEM TIF. METHODS: In this multicenter retrospective study, post-POEM patients with GER who underwent TIF were included. The study end points were: (i) technical success; (ii) safety; (iii) effectiveness (changes in symptoms, scores, proton pump inhibitor [PPI] use, pH studies). RESULTS: 12 patients underwent TIF after POEM, nine of whom had daily symptoms, with 91.7% requiring twice daily (BID) PPIs. Technical success was achieved in all patients. Two adverse events occurred. There were significant decreases in the percentage of patients on BID PPIs (P = 0.03), frequency of daily symptoms (P = 0.03), Reflux Severity Index questionnaire, and GERD Health-related Quality of Life scores (P = 0.03 and P = 0.003; n = 6). pH studies performed in seven of the patients showed a significant reduction in the mean DeMeester score (P = 0.05) and mean percentage acid exposure time (P = 0.04). CONCLUSION: Our experience suggests that TIF may be effective and safe in treating GER after POEM. Larger prospective trials are needed.

Zenker's peroral endoscopic myotomy, or flexible or rigid septotomy for Zenker's diverticulum: a multicenter retrospective comparison.

BACKGROUND: Treatment of Zenker's diverticulum has evolved from open surgery to endoscopic techniques, including flexible and rigid endoscopic septotomy, and more recently, peroral endoscopic myotomy (Z-POEM). This study compared the effectiveness of flexible and rigid endoscopic septotomy with that of Z-POEM. METHODS: Consecutive patients who underwent endoscopic septotomy (flexible/rigid) or Z-POEM for Zenker's diverticulum between 1/2016 and 9/2019 were included. Primary outcomes were clinical success (decrease in Dakkak and Bennett dysphagia score to ≤ 1), clinical failure, and clinical recurrence. Secondary outcomes included technical success and rate/severity of adverse events. RESULTS: 245 patients (110 females, mean age 72.63 years, standard deviation [SD] 12.37 years) from 12 centers were included. Z-POEM was the most common management modality (n = 119), followed by flexible (n = 86) and rigid (n = 40) endoscopic septotomy. Clinical success was 92.7 % for Z-POEM, 89.2 % for rigid septotomy, and 86.7 % for flexible septotomy (P = 0.26). Symptoms recurred in 24 patients (15 Z-POEM during a mean follow-up of 282.04 [SD 300.48] days, 6 flexible, 3 rigid [P = 0.47]). Adverse events occurred in 30.0 % rigid septotomy patients, 16.8 % Z-POEM patients, and 2.3 % flexible septotomy patients (P < 0.05). CONCLUSIONS: There was no difference in outcomes between the three treatment approaches for symptomatic Zenker's diverticulum. Rigid endoscopic septotomy was associated with the highest rate of complications, while flexible endoscopic septotomy appeared to be the safest. Recurrence following Z-POEM was similar to flexible and rigid endoscopic septotomy. Prospective studies with long-term follow-up are required.

Per Oral Endoscopic Myotomy for Zenker's Diverticulum: A Novel and Superior Technique Compared With Septotomy?

INTRODUCTION: Endoscopic management of Zenker diverticuli (ZD) has traditionally been via septotomy technique. The recent development of tunneling technique has shown to be both efficacious and safe. The aim of this study is to evaluate the tunneling technique using per oral endoscopic myotomy (Z-POEM) versus septotomy. METHODS: Patients who underwent endoscopic management of ZD either by Z-POEM or septotomy from March 2017 until November 2020 from 9 international academic centers were included. Demographics, clinical data preprocedure and postprocedure, procedure time, adverse events, and hospital length of stay were analyzed. RESULTS: A total of 101 patients (mean age 74.9 y old, 55.4% male) were included: septotomy (n=49), Z-POEM (n=52). Preprocedure Functional Oral Intake Scale score and Eckardt score was 5.3 and 5.4 for the septotomy group and 5.9 and 5.15 for the Z-POEM group. Technical success was achieved in 98% of the Z-POEM group and 100% of the septotomy group. Clinical success was achieved in 84% and 92% in the septotomy versus Z-POEM groups. Adverse events occurred in 30.6% (n=15) in septotomy group versus 9.6% (n=5) in the Z-POEM group (P=0.017). Reintervention for ongoing symptoms occurred in 7 patients in the septotomy group and 3 patients in the Z-POEM group. Mean hospital length of stay was shorter for the Z-POEM group, at 1.5 versus 1.9 days. CONCLUSIONS: A tunneling technique via the Z-POEM procedure is an efficacious and safe endoscopic treatment for ZD. Z-POEM is a safer procedure with a statistically significant reduction in adverse events compared with traditional septotomy technique.

Endoscopic Management of GERD.

Gastroesophageal reflux disease (GERD) has consistently been the most frequently diagnosed gastrointestinal malady in the USA. The mainstay of therapy has traditionally been medical management, including lifestyle and dietary modifications as well as antacid medications. In those patients found to be refractory to medical management or with a contraindication to medications, the next step up has been surgical anti-reflux procedures. Recently, though innovative advancements in therapeutic endoscopy have created numerous options for the endoscopic management of GERD, in this review, we discuss the various endoscopic therapy options, as well as suggested strategies we use to recommend the most appropriate therapy for patients.

Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial.

BACKGROUND: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. METHODS: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749. FINDINGS: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months. INTERPRETATION: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. FUNDING: Medtronic.

Comparison of Two Specialized Histology Needles for Endoscopic Ultrasound (EUS)-Guided Liver Biopsy: A Pilot Study.

BACKGROUND: EUS-guided liver biopsy (EUS-LB) has been shown to be a safe and effective alternative to percutaneous liver biopsy. The optimal needle device and technique for EUS-LB is still evolving. The aim of this study was to compare the efficacy of two second-generation 19G fine-needle biopsy (FNB) (Franseen- and Fork-tip) devices for EUS-LB. METHODS: This is a repeated-measure crossover study with a prospectively maintained cohort of patients. We performed EUS-LB with a one-pass and single-actuation method using two 19G FNB needles in 22 consecutive patients between 10/2018 and 9/2019. Patients were randomized to left vs right liver lobes to be biopsied as well as the needle sequence. The specimens obtained were evaluated for adequacy for histologic diagnosis. The primary outcome was number of complete portal tracts (CPTs), post-fix aggregate, and longest specimen length. Secondary outcomes were prefix aggregate specimen length and the specimen adequacy judged by two expert pathologists. RESULTS: A total of 44 liver biopsies were performed in 22 patients. The CPTs were higher in the Franseen-tip needle group compared to the Fork-tip needle group (14.4 vs 9.5, p = 0.043). Post-fix aggregate specimen length (44.9 mm vs 34.6 mm, p = 0.097), the post-fix longest specimen length (19.9 mm vs 13.7 mm, p = 0.175), and prefix aggregate specimen length (51.7 mm vs 45 mm, p = 0.265) were not significantly different. Both needles showed similarly high histologic adequacy (100% vs 95.5%, p = 0.312). Interestingly, the right of the liver showed higher yield of CPTs with both needles (Franseen, 16.2 vs. 12.8, p = 0.003, the Fork-tip, 12.8 vs. 7.0, p < 0.0001). CONCLUSION: EUS-guided liver biopsy using the 19G Franseen-tip needle may provide more CPTs than 19G Fork-tip needle on a single-pass, single-actuation comparison.

Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial.

BACKGROUND: Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. METHODS: SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. FINDINGS: Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; p<0·0001), office SBP -10·0 mm Hg (-15·1 to -4·9; p=0·0004), and office DBP -5·3 mm Hg (-7·8 to -2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP -0·5 mm Hg (95% CI -3·9 to 2·9; p=0·7644), 24-h DBP -0·4 mm Hg (-2·2 to 1·4; p=0·6448), office SBP -2·3 mm Hg (-6·1 to 1·6; p=0·2381), and office DBP -0·3 mm Hg (-2·9 to 2·2; p=0·8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0 to -1·5; p=0·0155), and office DBP -4·9 mm Hg (-8·5 to -1·4; p=0·0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group. INTERPRETATION: Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation. FUNDING: Medtronic.

Diabetes Mellitus and Prevention of Late Myocardial Infarction After Coronary Stenting in the Randomized Dual Antiplatelet Therapy Study.

BACKGROUND: Patients with diabetes mellitus (DM) are at high risk for recurrent ischemic events after coronary stenting. We assessed the effects of continued thienopyridine among patients with DM participating in the Dual Antiplatelet Therapy (DAPT) Study as a prespecified analysis. METHODS AND RESULTS: After coronary stent placement and 12 months treatment with open-label thienopyridine plus aspirin, 11 648 patients free of ischemic or bleeding events and who were medication compliant were randomly assigned to continued thienopyridine or placebo, in addition to aspirin, for 18 more months. After randomization, patients with DM (n=3391), in comparison with patients without DM (n=8257), had increased composite outcome of death, myocardial infarction (MI), or stroke (6.8% versus 4.3%, P<0.001), increased death (2.5% versus 1.4%, P<0.001), and MI (4.2% versus 2.6%, P<0.001). Among patients with DM, in a comparison of continued thienopyridine versus placebo, rates of stent thrombosis were 0.5% versus 1.1%, P=0.06, and rates of MI were 3.5% versus 4.8%, P=0.058; and among patients without DM the rates were 0.4% versus 1.4%, P<0.001 (stent thrombosis, P interaction=0.21) and 1.6% versus 3.6%, P<0.001 (MI, P interaction=0.02). Bleeding risk with continued thienopyridine was similar among patients with or without DM (interaction P=0.61). CONCLUSIONS: In patients with DM, continued thienopyridine beyond 1 year after coronary stenting is associated with reduced risk of MI, although this benefit is attenuated in comparison with patients without DM. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00977938.

Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents.

BACKGROUND: Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain. METHODS: Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug (clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding. RESULTS: A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo. Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis (0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85]; P<0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group (hazard ratio, 1.36 [95% CI, 1.00 to 1.85]; P=0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5% vs. 1.6%, P=0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment. CONCLUSIONS: Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. (Funded by a consortium of eight device and drug manufacturers and others; DAPT ClinicalTrials.gov number, NCT00977938.).

Invasive evaluation of patients with angina in the absence of obstructive coronary artery disease.

BACKGROUND: More than 20% of patients presenting to the cardiac catheterization laboratory with angina have no angiographic evidence of coronary artery disease. Despite a "normal" angiogram, these patients often have persistent symptoms, recurrent hospitalizations, a poor functional status, and adverse cardiovascular outcomes, without a clear diagnosis. METHODS AND RESULTS: In 139 patients with angina in the absence of obstructive coronary artery disease (no diameter stenosis >50%), endothelial function was assessed; the index of microcirculatory resistance, coronary flow reserve, and fractional flow reserve were measured; and intravascular ultrasound was performed. There were no complications. The average age was 54.0±11.4 years, and 107 (77%) were women. All patients had at least some evidence of atherosclerosis based on an intravascular ultrasound examination of the left anterior descending artery. Endothelial dysfunction (a decrease in luminal diameter of >20% after intracoronary acetylcholine) was present in 61 patients (44%). Microvascular impairment (an index of microcirculatory resistance ≥25) was present in 29 patients (21%). Seven patients (5%) had a fractional flow reserve ≤0.80. A myocardial bridge was present in 70 patients (58%). Overall, only 32 patients (23%) had no coronary explanation for their angina, with normal endothelial function, normal coronary physiological assessment, and no myocardial bridging. CONCLUSIONS: The majority of patients with angina in the absence of obstructive coronary artery disease have occult coronary abnormalities. A comprehensive invasive assessment of these patients at the time of coronary angiography can be performed safely and provides important diagnostic information that may affect treatment and outcomes.

Prasugrel plus aspirin beyond 12 months is associated with improved outcomes after TAXUS Liberté paclitaxel-eluting coronary stent placement.

BACKGROUND: The TAXUS Liberté Post Approval Study (TL-PAS) contributed patients treated with TAXUS Liberté paclitaxel-eluting stent and prasugrel to the Dual Antiplatelet Therapy Study (DAPT) that compared 12 and 30 months thienopyridine plus aspirin therapy after drug-eluting stents. METHODS AND RESULTS: Outcomes for 2191 TL-PAS patients enrolled into DAPT were assessed. The DAPT coprimary composite end point (death, myocardial infarction [MI], or stroke) was lower with 30 compared with 12 months prasugrel treatment (3.7% versus 8.8%; hazard ratio [HR], 0.407; P<0.001). Rates of death and stroke were similar between groups, but MI was significantly reduced with prolonged prasugrel treatment (1.9% versus 7.1%; HR, 0.255; P<0.001). The DAPT coprimary end point, stent thrombosis, was also lower with longer therapy (0.2% versus 2.9%; HR, 0.063; P<0.001). MI related to stent thrombosis (0% versus 2.6%; P<0.001) and occurring spontaneously (1.9% versus 4.5%; HR, 0.407; P=0.007) were both reduced with prolonged prasugrel. MI rates increased within 90 days of prasugrel cessation after both 12 and 30 months treatment. Composite Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) moderate or severe bleeds were modestly increased (2.4% versus 1.7%; HR, 1.438; P=0.234) but severe bleeds were not more frequent (0.3% versus 0.5%; HR, 0.549; P=0.471) in the prolonged treatment group. CONCLUSIONS: Prasugrel and aspirin continued for 30 months reduced ischemic events for the TAXUS Liberté paclitaxel-eluting stent patient subset from DAPT through reductions in MI and stent thrombosis. Withdrawal of prasugrel was followed by an increase in MI after both 12 and 30 months therapy. The optimal duration of dual antiplatelet therapy with prasugrel after TAXUS Liberté paclitaxel-eluting stent remains unknown, but appears to be >30 months. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00997503.

Predictors of blood pressure response in the SYMPLICITY HTN-3 trial.

AIMS: The SYMPLICITY HTN-3 randomized, blinded, sham-controlled trial confirmed the safety of renal denervation (RDN), but did not meet its primary efficacy endpoint. Prior RDN studies have demonstrated significant and durable reductions in blood pressure. This analysis investigated factors that may help explain these disparate results. METHODS AND RESULTS: Patients with resistant hypertension were randomized 2 : 1 to RDN (n = 364) or sham (n = 171). The primary endpoint was the difference in office systolic blood pressure (SBP) change at 6 months. A multivariable analysis identified predictors of SBP change. Additional analyses examined the influence of medication changes, results in selected subgroups and procedural factors. Between randomization and the 6-month endpoint, 39% of patients underwent medication changes. Predictors of office SBP reduction at 6 months were baseline office SBP ≥ 180 mmHg, aldosterone antagonist use, and non-use of vasodilators; number of ablations was a predictor in the RDN group. Non-African-American patients receiving RDN had a significantly greater change in office SBP than those receiving sham; -15.2 ± 23.5 vs. -8.6 ± 24.8 mmHg, respectively (P = 0.012). Greater reductions in office and ambulatory SBP, and heart rate were observed with a higher number of ablations and energy delivery in a four-quadrant pattern. CONCLUSIONS: Post hoc analyses, although derived from limited patient cohorts, reveal several potential confounding factors that may partially explain the unexpected blood pressure responses in both the sham control and RDN groups. These hypothesis-generating data further inform the design of subsequent research to evaluate the potential role of RDN in the treatment of resistant hypertension. CLINICALTRIALS.GOV IDENTIFIER: NCT01418261.

Antiplatelet therapy duration following bare metal or drug-eluting coronary stents: the dual antiplatelet therapy randomized clinical trial.

IMPORTANCE: Despite antirestenotic efficacy of coronary drug-eluting stents (DES) compared with bare metal stents (BMS), the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Although dual antiplatelet therapy (DAPT) beyond 1 year provides ischemic event protection after DES, ischemic event risk is perceived to be less after BMS, and the appropriate duration of DAPT after BMS is unknown. OBJECTIVE: To compare (1) rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE; composite of death, myocardial infarction, or stroke) after 30 vs 12 months of thienopyridine in patients treated with BMS taking aspirin and (2) treatment duration effect within the combined cohorts of randomized patients treated with DES or BMS as prespecified secondary analyses. DESIGN, SETTING, AND PARTICIPANTS: International, multicenter, randomized, double-blinded, placebo-controlled trial comparing extended (30-months) thienopyridine vs placebo in patients taking aspirin who completed 12 months of DAPT without bleeding or ischemic events after receiving stents. The study was initiated in August 2009 with the last follow-up visit in May 2014. INTERVENTIONS: Continued thienopyridine or placebo at months 12 through 30 after stent placement, in 11,648 randomized patients treated with aspirin, of whom 1687 received BMS and 9961 DES. MAIN OUTCOMES AND MEASURES: Stent thrombosis, MACCE, and moderate or severe bleeding. RESULTS: Among 1687 patients treated with BMS who were randomized to continued thienopyridine vs placebo, rates of stent thrombosis were 0.5% vs 1.11% (n = 4 vs 9; hazard ratio [HR], 0.49; 95% CI, 0.15-1.64; P = .24), rates of MACCE were 4.04% vs 4.69% (n = 33 vs 38; HR, 0.92; 95% CI, 0.57-1.47; P = .72), and rates of moderate/severe bleeding were 2.03% vs 0.90% (n = 16 vs 7; P = .07), respectively. Among all 11,648 randomized patients (both BMS and DES), stent thrombosis rates were 0.41% vs 1.32% (n = 23 vs 74; HR, 0.31; 95% CI, 0.19-0.50; P < .001), rates of MACCE were 4.29% vs 5.74% (n = 244 vs 323; HR, 0.73; 95% CI, 0.62-0.87; P < .001), and rates of moderate/severe bleeding were 2.45% vs 1.47% (n = 135 vs 80; P < .001). CONCLUSIONS AND RELEVANCE: Among patients undergoing coronary stent placement with BMS and who tolerated 12 months of thienopyridine, continuing thienopyridine for an additional 18 months compared with placebo did not result in statistically significant differences in rates of stent thrombosis, MACCE, or moderate or severe bleeding. However, the BMS subset may have been underpowered to identify such differences, and further trials are suggested. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00977938.

A novel, proof-of-concept radiofrequency renal denervation strategy to improve procedural efficiency: 12-month results from the SPYRAL DYSTAL pilot study.

BACKGROUND: Catheter-based renal sympathetic denervation (RDN) reduced blood pressure (BP) in multiple randomized sham-controlled trials of patients with uncontrolled hypertension (HTN). We tested proof-of-concept for a more selective treatment strategy, exclusively targeting these areas to improve the efficiency of the procedure. METHODS: The SPYRAL DYSTAL Pilot study was designed to mirror the SPYRAL HTN-OFF MED Pivotal study, enabling comparison with a propensity score adjusted active-control group. Patients were antihypertensive medication-free for one month before undergoing BP assessment. Those with office BP of 150-180/>90 mmHg and with an ambulatory systolic BP of 140-170 mmHg were selected to undergo open label treatment, delivering energy only to the distal main renal arteries and first order branches. Patients from DYSTAL were compared with patients who underwent maximized RF RDN treatment in the prior randomized OFF MED trial at 3 months. After 3 months, patients resumed antihypertensive medications as indicated. Safety and efficacy outcomes were assessed post hoc through 12 months. RESULTS: The SPYRAL DYSTAL Pilot study treated 56 HTN patients. Baseline office systolic BP (OSBP) and 24-h ambulatory systolic BP (ASBP) were similar between DYSTAL and OFF MED patient groups. The number of ablations (32.3 ± 8.0 vs 46.6 ± 15.3, p < 0.001), procedure time (67 ± 21 min vs 99 ± 36 min; p < 0.001), and contrast volume (173 ± 77 cc vs 208 ± 96 cc; p = 0.014) were significantly lower with the simplified treatment strategy. OSBP and ASBP changes compared with baseline were -9.0 and -1.4 mmHg at 3 months, -20.3 and -13.9 mmHg at 6 months, and -20.3 and -16.6 mmHg at 12 months, respectively. During the medication up-titration phase, BP reductions among DYSTAL patients were similar to reductions observed in OFF MED through 12 months, with comparable number of drugs (1.4 and 1.5 medications, respectively (P=NS)). Two adverse events related to guidewire placement were reported. CONCLUSION: In this pilot study, focusing ablation treatment on the distal main and proximal branch renal arteries was performed, resulting in fewer RF lesions, and reduced contrast volume and procedure time. Whether BP reductions are similar between a selective vs. maximized RDN approach requires further prospective study.

Endoscopic Ultrasound-Guided Gallbladder Drainage Versus Percutaneous Drainage in Patients With Acute Cholecystitis Undergoing Elective Cholecystectomy.

INTRODUCTION: Cholecystectomy (CCY) is the gold standard treatment of acute cholecystitis (AC). Nonsurgical management of AC includes percutaneous transhepatic gallbladder drainage (PT-GBD) and endoscopic ultrasound-guided gallbladder drainage (EUS-GBD). This study aims to compare outcomes of patients who undergo CCY after having received EUS-GBD vs PT-GBD. METHODS: A multicenter international study was conducted in patients with AC who underwent EUS-GBD or PT-GBD, followed by an attempted CCY, between January 2018 and October 2021. Demographics, clinical characteristics, procedural details, postprocedure outcomes, and surgical details and outcomes were compared. RESULTS: One hundred thirty-nine patients were included: EUS-GBD in 46 patients (27% male, mean age 74 years) and PT-GBD in 93 patients (50% male, mean age 72 years). Surgical technical success was not significantly different between the 2 groups. In the EUS-GBD group, there was decreased operative time (84.2 vs 165.4 minutes, P < 0.00001), time to symptom resolution (4.2 vs 6.3 days, P = 0.005), and length of stay (5.4 vs 12.3 days, P = 0.001) compared with the PT-GBD group. There was no difference in the rate of conversion from laparoscopic to open CCY: 5 of 46 (11%) in the EUS-GBD arm and 18 of 93 (19%) in the PT-GBD group ( P value 0.2324). DISCUSSION: Patients who received EUS-GBD had a significantly shorter interval between gallbladder drainage and CCY, shorter surgical procedure times, and shorter length of stay for the CCY compared with those who received PT-GBD. EUS-GBD should be considered an acceptable modality for gallbladder drainage and should not preclude patients from eventual CCY.

Safety and Efficacy of Renal Denervation in Patients Taking Antihypertensive Medications.

BACKGROUND: Renal denervation (RDN) reduces blood pressure (BP) in patients with uncontrolled hypertension in the absence of antihypertensive medications. OBJECTIVES: This trial assessed the safety and efficacy of RDN in the presence of antihypertensive medications. METHODS: SPYRAL HTN-ON MED is a prospective, randomized, sham-controlled, patient- and assessor-blinded trial enrolling patients from 56 clinical centers worldwide. Patients were prescribed 1 to 3 antihypertensive medications. Patients were randomized to radiofrequency RDN or sham control procedure. The primary efficacy endpoint was the baseline-adjusted change in mean 24-hour ambulatory systolic BP at 6 months between groups using a Bayesian trial design and analysis. RESULTS: The treatment difference in the mean 24-hour ambulatory systolic BP from baseline to 6 months between the RDN group (n = 206; -6.5 ± 10.7 mm Hg) and sham control group (n = 131; -4.5 ± 10.3 mm Hg) was -1.9 mm Hg (95% CI: -4.4 to 0.5 mm Hg; P = 0.12). There was no significant difference between groups in the primary efficacy analysis with a posterior probability of superiority of 0.51 (Bayesian treatment difference: -0.03 mm Hg [95% CI: -2.82 to 2.77 mm Hg]). However, there were changes and increases in medication intensity among sham control patients. RDN was associated with a reduction in office systolic BP compared with sham control at 6 months (adjusted treatment difference: -4.9 mm Hg; P = 0.0015). Night-time BP reductions and win ratio analysis also favored RDN. There was 1 adverse safety event among 253 assessed patients. CONCLUSIONS: There was no significant difference between groups in the primary analysis. However, multiple secondary endpoint analyses favored RDN over sham control. (SPYRAL HTN-ON MED Study [Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications]; NCT02439775).

Rationale and design of the TAXUS Liberte Post-Approval Study: examination of patients receiving the TAXUS Liberté stent with concomitant prasugrel therapy in routine interventional cardiology practice.

BACKGROUND: Observational studies of new coronary stents are necessary to assess performance in a variety of complex patient and lesion types. Furthermore, the optimal dose and duration of thienopyridine treatment is unclear, particularly in patients with complex clinical conditions. The TAXUS Liberte Post-Approval Study is designed to provide 5-year data on the TAXUS Liberté paclitaxel-eluting stent with concomitant prasugrel therapy in routine clinical practice and to contribute data to the DAPT study. STUDY DESIGN: The TAXUS Liberte Post-Approval Study is a prospective, multicenter, observational study. Enrollment of approximately 4,200 patients receiving ≥1 TAXUS Liberté stents is planned. All patients without a contraindication will be prescribed prasugrel plus aspirin for 1 year. The 12-month primary end point of cardiac death or myocardial infarction in on-label stent patients will be compared with historical TAXUS Express stent data from the TAXUS ATLAS and TAXUS ARRIVE studies. Secondary clinical end points include stent thrombosis, all-cause death, stroke, revascularization, and bleeding in all patients. In addition, this study will be the first to evaluate prasugrel use in a routine practice setting (including 5 and 10 mg daily doses) and will contribute data to the DAPT Study, comparing 12 versus 30 months of dual antiplatelet therapy after drug-eluting stent placement. SUMMARY: The TAXUS Liberte Post-Approval Study will be the first to provide long-term real-world data on use of the TAXUS Liberté Stent with prasugrel treatment. The study is currently enrolling, and primary end point data are expected in mid 2013.

Most accurate definition of a high femoral artery puncture: aiming to better predict retroperitoneal hematoma in percutaneous coronary intervention.

BACKGROUND: Retroperitoneal hematoma (RPH) increases morbidity and mortality in percutaneous coronary intervention (PCI). High femoral arteriotomy is an independent predictor of RPH, but the optimal angiographic criterion for defining a high puncture is unknown. METHODS: We retrospectively identified 557 consecutive PCI cases with femoral angiograms. Arteriotomy sites were categorized as high based on three angiographic criteria: at or above the proximal third of the femoral head (criterion A), at or above the most inferior border of the inferior epigastric artery (criterion B), and at or above the origin of the inferior epigastric artery (criterion C). Cases of RPH were then identified. RESULTS: Of the 557 PCI patients, 26 had a high femoral arteriotomy by criterion A, 17 by criterion B, and 6 by criterion C. Among these patients with a high arteriotomy, RPH occurred in four with criterion A, in three with criterion B, and in one with criterion C. Of the three criteria, criterion A most strongly correlated with RPH (odds ratio [OR] 96, 95% confidence interval [CI] 10.3-898.4; p < 0.0001) compared with criterion B (OR 58, 95% CI 8.9 to 372.6; p < 0.0001) or C (OR 27, 95% CI 2.6 to 290.1; p = 0.053). All criteria had high specificity (A, 96%; B, 97%; C, 99%), but the sensitivity was higher with criterion A (80%) than criterion B (60%) or C (20%), and statistically, the use of criterion A led to the most accurate risk-stratification for RPH (A, κ = 0.79; B, κ = 0.59; C, κ = 0.19). CONCLUSIONS: Among the three common definitions of high arteriotomy, femoral artery puncture at or above the proximal third of the femoral head is the landmark that most accurately risk stratifies PCI patients for development of RPH.

Histological evidence supporting the durability of successful radiofrequency renal denervation in a normotensive porcine model.

BACKGROUND: Sustained blood pressure reductions after radiofrequency (RF) renal denervation (RDN) have been reported to 3 years in patients with uncontrolled hypertension. However, mechanistic data to support procedural durability are lacking. We aimed to quantify the long-term nerve anatomic and functional effects of RF RDN in a preclinical model. METHODS: Bilateral RF RDN was performed in 20 normotensive swine. Renal tissue samples were obtained in the RDN-treated groups at 7 ( n  = 6), 28 ( n  = 6), and 180 days ( n  = 8) postprocedure for quantification of cortical norepinephrine (NE) levels and renal cortical axon density. Tissue fibrosis, necrosis and downstream nerve fiber atrophy (axonal loss) were also scored for each sample. Three additional untreated groups ( n  = 6, n  = 6 and n  = 8, respectively) served as control. RESULTS: Pathologic nerve changes were characterized by necrosis in the ablated region at 7 days that partially resolved by 28 days and fully resolved at 180 days. Axonal loss was apparent within and downstream to the ablation regions and was evident at 7, 28 and 180 days in the main vessel and branch vessels. Consequently, renal cortical axon density and corresponding cortical NE levels were significantly reduced at 7 days in the RDN vs. control group and remained suppressed at 180 days. CONCLUSIONS: Reductions in renal NE, cortical axon density and downstream axonal loss caused by axonal destruction persisted through 180 days post-RDN in a normotensive swine model. These results suggest functional nerve regrowth after RF RDN is unlikely and support published clinical evidence that the procedure results in durable blood pressure reduction.